The main objective of this project is to understand the control mechanisms of growth and differentiation of neuroblastoma cells in culture. Such a study may aid in developing new approaches to the therapy of neuroblastoma tumors. The role of cyclic GMP in the regulation of differentiated function in neuroblastoma cells will be studied. The intracellular level of cyclic GMP will be measured under conditions which increase the intracellular level of cyclic AMP. The regulation of cyclic GMP phosphodiesterase activity in neuroblastoma cells will be studied and compared with that of cyclic AMP phosphodiesterase activity. Although acetylcholine stimulates adenylate cyclase activity in vitro, it decreases the intracellular level of cAMP stimulated by inhibitor of phosphodiesterase in vivo. Therefore the mechanism of inhibitory-effect of acetylcholine on the cyclic AMP will be studied.